Method for treating IgE-mediated disorders

Abstract

The present invention relates to a method for adjusting the affinity of a polypeptide to a target molecule by a combination of steps, including: (1) the identification of aspartyl residues which are prone to isomerization; (2) the substitution of alternative residues and screening the resulting mutants for affinity against the target molecule. In a preferred embodiment, the method of subtituting residues is affinity maturation with phage display (AMPD). In a further preferred embodiment the polypeptide is an antibody and the target molecule is an antigen. In a further preferred embodiment, the antibody is anti-IgE and the target molecule is IgE. In another embodiment, the invention relates to an anti-IgE antibody having improved affinity to IgE.

1. A method of inhibiting the binding of IgE to the high affinity receptor FcεRI to treat an IgE-mediated disorder comprising administering a therapeutically effective amount of an humanized anti-IgE antibody or IgE binding fragment thereof selected from the group consisting of:
 (a) a molecule comprising the variable heavy and variable light chains of E26 (SEQ ID NOS:12 and 8); 
 (b) a molecule comprising the variable heavy and variable light chains of E27 (SEQ ID NOS:11 and 8) or 
 (c) antigen binding fragments of (a) or (b). 
 
     
     
       2. The method of  claim 1 , wherein the IgE mediated disorder is hypersensitivity. 
     
     
       3. The method of  claim 2 , wherein the IgE mediated disorder is anaphylactic hypersensitivity. 
     
     
       4. The method of  claim 3 , wherein the anaphylaxis is caused by bee sting. 
     
     
       5. The method of  claim 3 , wherein the anaphylaxis is caused by snake bite. 
     
     
       6. The method of  claim 3 , wherein the anaphylaxis is caused by the administration of parental medication. 
     
     
       7. The method of  claim 3 , wherein the anaphylactic hypersensitivity results from exposure to an allergen selected from the group consisting of: pollen, food, dust mites, animal dander, fungal spores and insect venom. 
     
     
       8. The method of  claim 1 , wherein the IgE-mediated disorder is selected from the group consisting of asthma, allergic rhinitis, eczema, urticaria and food allergy. 
     
     
       9. The method of  claim 7 , wherein the allergen is pollen. 
     
     
       10. The method of  claim 7 , wherein the allergen is food. 
     
     
       11. The method of  claim 7 , wherein the allergen is dust mites. 
     
     
       12. The method of  claim 7 , wherein the allergen is animal dander. 
     
     
       13. The method of  claim 7 , wherein the allergen is fungal spores. 
     
     
       14. The method of  claim 7 , wherein the allergen is insect venom. 
     
     
       15. The method of  claim 8 , wherein the IgE-mediated disorder is asthma. 
     
     
       16. The method of  claim 8 , wherein the IgE-mediate disorder is allergic rhinitis. 
     
     
       17. The method of  claim 8 , wherein the IgE-mediated disorder is urticaria. 
     
     
       18. The method of  claim 8 , wherein the IgE-mediated disorder is food allergy.